AB0567 SHORT AND LONG-TERM RENAL OUTCOMES OF PATIENTS WITH PROLIFERATIVE LUPUS NEPHRITIS: DATA FROM A SINGLE INSTITUTE INCEPTION COHORT.
Authors: E. Kapsia, S. Marinaki, I. Michelakis, G. Liapis, P. Sfikakis, J. N. Boletis, M. Tektonidou
Journal: Annals of the Rheumatic Diseases (2022)

Background Renal involvement in SLE is associated with high risk of morbidity with proliferative lupus nephritis (PLN) having the worst prognosis. Although advances in immunosuppressive treatment led to better renal survival rates, response to treatment and short- and long-term outcomes differ among cohorts. Objectives To evaluate short and long term renal outcomes in an inception cohort of patients with PLN. We also aimed to define clinical, laboratory, histological and treatment determinants of partial (PR) or complete response (CR), flare, and long-term renal and patient survival. Methods An inception cohort of 83 patients with biopsy-proven PLN (class III, IV, or III/IV+V)(diagnosed between 1992 and 2019) was retrospectively studied. Data collected included histologic characteristics at baseline, demographic, clinical, laboratory, and therapeutic parameters at baseline, 6-9-12-18-24-36-72 months after PLN diagnosis, time of renal flare and last follow-up visit. Univariate logistic and Cox regression analyses were performed to estimate response to treatment, flare and long-term renal survival. Variables found to be significant in the univariate analyses were included in the multivariate models. Results Mean age of the patients was 43±12 years, 78% were women, 96% were Caucasians and median duration of SLE before PLN diagnosis was 12 months (IQR 60).Mean SLEDAI score at PLN diagnosis was 12.8±4 and mean proteinuria was 3.69±3.3g/d. At baseline, 73.5% (61/83) had eGFR&gt;60ml/min/1.73m 2 , 15.5% (13/83) eGFR 30-60 and 11% (9/83) eGFR&lt;30. 32% (27/83)of patients had class III LN, 46% (38/83) IV, and 22% (18/83) III/IV+V. Median follow-up time was 107 months(IQR 94). Induction immunosuppressive treatment consisted of cyclophosphamide (CYC) in 71% (59/83) of patients (12/59 in combination with rituximab (RTX)), mycophenolic acid (MPA) in 25% (21/83)(2/21 in combination with RTX) and RTX alone in 2 patients. 1 patient did not receive any immunosuppressive treatment due to ESRD. Patients treated with CYC had a higher baseline SLEDAI score, lower C3 and C4 levels, higher biopsy activity index and higher proteinuria levels than those treated with MPA. 76% (63/83) received MPA as maintenance treatment, 8% (7/83) azathioprine, 7% (6/83) CYC and 8% (7/83) did not receive any maintenance regimen (3/7 due to ESRD, 2/7 received RTX as induction and continued with steroids only, 1/7 due to non-compliance, 1/7 lost to follow-up after 6months). Median duration of treatment was 43.6 months (IQR 44.6). 66% of patients had response (CR or PR) at 6 months (43% CR, 23% PR), 73% at 9 months (46%CR, 27% PR), 77% at 12 months (61%CR, 16%PR) and 91% at the end of follow-up (80%CR, 11%PR)(Figure 1). Median time to complete remission was 9 months (IQR 14) and median time to partial remission was 4 months (IQR 7). In multivariate analysis, baseline eGFR&gt;60ml/min correlated with shorter time to remission (HR 1.7, p=0.05). No clinical, laboratory or histological (PLN class, activity/chronicity index, number of crescents) parameters or any of induction immunosuppressives could predict time to remission. Figure 1. 38.5% of patients (32/83) had ≥1 renal flare in a median time of 40.5 months (IQR 44). In multivariate analysis, proteinuria &gt;1g/d at 12 months correlated significantly with risk of flare (OR 3.65, p=0.039), while induction treatment with MPA was associated with lower risk of flare compared to CYC (OR 0.21, p=0.031) (in combination or not with RTX). At a median follow-up time of 107 months, 2 patients died, 15.6% (13/83) developed chronic kidney disease (CKD) (&lt;60ml/min/1.73m 2 ), and 9.6% (8/83) ESRD. In multivariate analysis, baseline eGFR&lt;60ml/min (OR 14.0, p=0.02) and 12-month proteinuria &gt;1g/d (OR 12.0, p=0.02) were the only predictors of CKD. Conclusion In our inception cohort of patients with PLN, 66% of patients achieved response at 6 months, 77% at 12 months and 91% at the end of follow-up. Proteinuria &gt;1g/d at 12 months emerged as an important risk factor of renal flare and CKD, while MPA treatment was associated with lower risk of renal flare. Disclosure of Interests None declared